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A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma.

Abstract：

:The mitogen-activated protein (MAP) kinases mediate the response of renal glomerular mesangial cells to a variety of physiologic and pathologic stimuli. This investigation examines the effect of the cyclopentenone prostaglandin 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) on MAP kinases in human mesangial cells. We show that 15d-PGJ2 dose-dependently increases the extracellular signal-regulated kinase (ERK) activity of human mesangial cells, but has no effect on Jun-NH2-terminal kinase or p38 MAP kinase. Despite the fact that 15d-PGJ2 is a peroxisome proliferator-activated receptor (PPAR) ligand, and PPARgamma is shown to be expressed by mesangial cells, the thiazolidinedione PPARgamma agonist ciglitazone does not activate ERK. Additionally, a synthetic PPARgamma antagonist does not attenuate the activation of ERK by 15d-PGJ2. 15d-PGJ2-mediated ERK activation is however blocked by the MEK inhibitor PD 098059, appears to require phosphatidylinositol-3 kinase, but is independent of protein kinase C activation. These results demonstrate a novel effect of 15d-PGJ2 to induce ERK in human mesangial cells independently of PPARgamma.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Wilmer WA,Dixon C,Lu L,Hilbelink T,Rovin BH

doi

10.1006/bbrc.2001.4301

subject

Has Abstract

pub_date

2001-02-16 00:00:00

pages

57-62

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(01)94301-3

journal_volume

281

pub_type

杂志文章

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